tbuckley/cabot-search huggingface dataset:
Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings
Authors: Chul-min Lee, Eileen L. Yoon, Mimi Kim, Bo-Kyeong Kang, Seon Cho, Eun-Hee Nah, Dae Won Jun
Journal: Hepatology (2023)

In relation to the new umbrella terminology for steatotic liver disease (SLD), we aimed to elucidate the prevalence, distribution, and clinical characteristics of the SLD subgroups in the primary care setting.
Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma
Authors: Ankush Bhatia, Raquel Moreno, Anne S. Reiner, Subhiksha Nandakumar, Henry S. Walch, Teena M. Thomas, Philip J. Nicklin, Ye Choi, Anna Skakodub, Rachna Malani, Vivek Prabhakaran, Pallavi Tiwari, Maria Diaz, Katherine S. Panageas, Ingo K. Mellinghoff, Tejus A. Bale, Robert J. Young
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Isocitrate dehydrogenase–mutant (IDH-mt) gliomas are incurable primary brain tumors characterized by a slow-growing phase over several years followed by a rapid-growing malignant phase. We hypothesized that tumor volume growth rate (TVGR) on MRI may act as an earlier measure of clinical benefit during the active surveillance period. Experimental Design: We integrated three-dimensional volumetric measurements with clinical, radiologic, and molecular data in a retrospective cohort of IDH-mt gliomas that were observed after surgical resection in order to understand tumor growth kinetics and the impact of molecular genetics. Results: Using log-linear mixed modeling, the entire cohort (n = 128) had a continuous %TVGR per 6 months of 10.46% [95% confidence interval (CI), 9.11%–11.83%] and a doubling time of 3.5 years (95% CI, 3.10–3.98). High molecular grade IDH-mt gliomas, defined by the presence of homozygous deletion of CDKN2A/B, had %TVGR per 6 months of 19.17% (95% CI, 15.57%–22.89%) which was significantly different from low molecular grade IDH-mt gliomas with a growth rate per 6 months of 9.54% (95% CI, 7.32%–11.80%; P &amp;lt; 0.0001). Using joint modeling to comodel the longitudinal course of TVGR and overall survival, we found each one natural logarithm tumor volume increase resulted in more than a 3-fold increase in risk of death (HR = 3.83; 95% CI, 2.32–6.30; P &amp;lt; 0.0001). Conclusions: TVGR may be used as an earlier measure of clinical benefit and correlates well with the WHO 2021 molecular classification of gliomas and survival. Incorporation of TVGR as a surrogate endpoint into future prospective studies of IDH-mt gliomas may accelerate drug development.
Estradiol mediates colonic epithelial protection in aged mice after stroke and is associated with shifts in the gut microbiome
Authors: Juneyoung Lee, Pedram Peesh, Victoria Quaicoe, Chunfeng Tan, Anik Banerjee, Patrick Mooz, Bhanu P. Ganesh, Joseph Petrosino, Robert M. Bryan, Louise D. McCullough, Venugopal Reddy Venna
Journal: Gut Microbes (2023)

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young males, but not in young females after experimental stroke. In contrast, mucin-related genes were enhanced in young females and contributed to mucus formation that maintains the distance between the host and gut bacteria. Bacterial community profiling was done using universal amplification of 16S rRNA gene sequences. The sex-specific colonic epithelial defense responses after stroke in young females were reversed with ovariectomy and led to a shift from a predominately mucin response to the enhanced AMP expression seen in males after stroke. Estradiol (E2) replacement prior to stroke in aged females increased mucin gene expression in the colonic ECs. Interestingly, we found that E2 treatment reduced stroke-associated neuronal hyperactivity in the insular cortex, a brain region that interacts with visceral organs such as the gut, in parallel to an increase in the composition of Lactobacillus and Bifidobacterium in the gut microbiota. This is the first study demonstrating sex differences in host defense mechanisms in the gut after brain injury.
Occupational physical activity and risk of mortality in women and men: the Tromsø Study 1986–2021
Authors: Edvard H Sagelv, Knut Eirik Dalene, Anne Elise Eggen, Ulf Ekelund, Marius Steiro Fimland, Kim Arne Heitmann, Andreas Holtermann, Kristoffer Robin Johansen, Maja-Lisa Løchen, Bente Morseth, Tom Wilsgaard
Journal: British Journal of Sports Medicine (2023)

Objective Associations between occupational physical activity (OPA) and mortality risks are inconclusive. We aimed to examine associations between (1) OPA separately and (2) jointly with leisure time physical activity (LTPA), and risk of all-cause, cardiovascular disease (CVD) and cancer mortality, over four decades with updated exposure and covariates every 6–8 years. Methods Adults aged 20–65 years from the Tromsø Study surveys Tromsø3-Tromsø7 (1986–2016) were included. We categorised OPA as low (sedentary), moderate (walking work), high (walking+lifting work) or very high (heavy manual labour) and LTPA as inactive, moderate and vigorous. We used Cox/Fine and Gray regressions to examine associations, adjusted for age, body mass index, smoking, education, diet, alcohol and LTPA (aim 1 only). Results Of 29 605 participants with 44 140 total observations, 4131 (14.0%) died, 1057 (25.6%) from CVD and 1660 (40.4%) from cancer, during follow-up (median: 29.1 years, 25th–75th: 16.5.1–35.3). In men, compared with low OPA, high OPA was associated with lower all-cause (HR 0.83, 95% CI 0.74 to 0.92) and CVD (subdistributed HR (SHR) 0.68, 95% CI 0.54 to 0.84) but not cancer mortality (SHR 0.99, 95% CI 0.84 to 1.19), while no association was observed for moderate or very high OPA. In joint analyses using inactive LTPA and low OPA as reference, vigorous LTPA was associated with lower all-cause mortality combined with low (HR 0.75, 95% CI 0.64 to 0.89), high (HR 0.67, 95% CI 0.54 to 0.82) and very high OPA (HR 0.74, 95% CI 0.58 to 0.94), but not with moderate OPA. In women, there were no associations between OPA, or combined OPA and LTPA, with mortality. Conclusion High OPA, but not moderate and very high OPA, was associated with lower all-cause and CVD mortality risk in men but not in women. Vigorous LTPA was associated with lower mortality risk in men with low, high and very high OPA, but not moderate OPA.
Quantifying the impact of immunotherapy on RNA dynamics in cancer
Authors: Ieva Usaite, Dhruva Biswas, Krijn Dijkstra, Thomas BK Watkins, Oriol Pich, Clare Puttick, Mihaela Angelova, Krupa Thakkar, Crispin Hiley, Nicolai Birkbak, Marleen Kok, Simone Zaccaria, Yin Wu, Kevin Litchfield, Charles Swanton, Nnennaya Kanu
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance. Methods We assembled a cohort of longitudinal pre-therapy and on-therapy samples from 174 patients treated with CPI across six cancer types by leveraging transcriptomic sequencing data from five studies. Results Meta-analyses of published RNA markers revealed an on-therapy pattern of immune reinvigoration in patients with breast cancer, which was not discernible pre-therapy, providing biological insight into the impact of CPI on the breast cancer immune microenvironment. We identified 98 breast cancer-specific correlates of CPI response, including 13 genes which are known IO targets, such as toll-like receptors TLR1 , TLR4 , and TLR8 , that could hold potential as combination targets for patients with breast cancer receiving CPI treatment. Furthermore, we demonstrate that a subset of response genes identified in breast cancer are already highly expressed pre-therapy in melanoma, and additionally we establish divergent RNA dynamics between breast cancer and melanoma following CPI treatment, which may suggest distinct immune microenvironments between the two cancer types. Conclusions Overall, delineating longitudinal RNA dynamics following CPI therapy sheds light on the mechanisms underlying diverging response trajectories, and identifies putative targets for combination therapy.
PER2 binding to HSP90 enhances immune response against oral squamous cell carcinoma by inhibiting IKK/NF-κB pathway and PD-L1 expression
Authors: Zhiwei Zhang, Deping Sun, Hong Tang, Jie Ren, Shilin Yin, Kai Yang
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Programmed death-ligand 1 (PD-L1) contributes to the immune escape of tumor cells and is a critical target for antitumor immunotherapy. However, the molecular mechanisms regulating PD-L1 expression remain unclear, hindering the development of effective therapies. Here we investigate the role and molecular mechanism of the core clock gene Period2 (PER2) in regulating PD-L1 expression and its role in the combination therapy of oral squamous cell carcinoma (OSCC). Methods Quantitative real-time PCR, western blotting or immunohistochemistry to detect expression of PER2 and PD-L1 in OSCC tissues and cells. Overexpression and knockdown of PER2 detects the function of PER2. Bioinformatics, immunoprecipitation, GST pull-down, CHX chase assay and western blot and strip to detect the mechanism of PER2 regulation for PD-L1. A humanized immune reconstitution subcutaneous xenograft mouse model was established to investigate the combination therapy efficacy. Results In OSCC tissues and cells, PER2 expression was reduced and PD-L1 expression was increased, the expression of PER2 was significantly negatively correlated with PD-L1. In vitro and in vivo experiments demonstrated that PER2 inhibited PD-L1 expression and enhanced T-cell-mediated OSCC cell killing by suppressing the IKK/NF-κB pathway. Mechanistically, PER2 binds to heat shock protein 90 (HSP90) through the PAS1 domain and reduces the interaction of HSP90 with inhibitors of kappa B kinase (IKKs), promoting the ubiquitination of IKKα/β and p65 nuclear translocation to inhibit IKK/NF-κB pathway, thereby suppressing PD-L1 expression. In humanized immune reconstitution subcutaneous xenograft mouse model, it was demonstrated that PER2 targeting combined with anti-PD-L1 treatment improved the inhibition of OSCC growth by promoting CD8 + T-cell infiltration into the tumor. Conclusions Our findings reveal the role and mechanism of PD-L1 regulation by PER2 and support the potential clinical application of PER2 targeting in combination with anti-PD-L1 in OSCC immunotherapy.
Fecal short-chain fatty acids in non-constipated irritable bowel syndrome: a potential clinically relevant stratification factor based on catabotyping analysis
Authors: Giorgio Gargari, Giacomo Mantegazza, Valentina Taverniti, Claudio Gardana, Alice Valenza, Federico Rossignoli, Maria Raffaella Barbaro, Giovanni Marasco, Cesare Cremon, Giovanni Barbara, Simone Guglielmetti
Journal: Gut Microbes (2023)

The gut microbiota is believed to be a critical factor in the pathogenesis of IBS, and its metabolic byproducts, such as short-chain fatty acids (SCFAs), are known to influence gut function and host health. Despite this, the precise role of SCFAs in IBS remains a topic of debate. In this study, we examined the bacterial community structure by 16S rRNA gene profiling and SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n = 100) and non-constipated patients (IBS-D and IBS-M; NC-IBS; n = 240) enrolled in 19 hospitals in Italy. Our findings suggest a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC exhibiting higher intra-sample biodiversity. Furthermore, we were able to classify non-constipated patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotype “high” and “low”), each characterized by unique taxonomic bacterial signatures. Our results suggest that the fecal catabotype with higher SCFA levels may represent a distinct clinical phenotype of IBS that could have implications for its diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, underscoring the importance of personalized strategies for its management.
Meta-Analytic Evidence for Association of Adversity With Brain Function
Authors: Dylan G. Gee, Alexis Brieant
Journal: JAMA Network Open (2023)

Niki Hosseini-Kamkar, PhD; Mahdieh Varvani Farahani, BSc; Maja Nikolic, BSc; Kaycee Stewart, MSc; Samantha Goldsmith, MSc; Mahdie Soltaninejad, MSc; Reza Rajabli, MSc; Cassandra Lowe, PhD; Andrew A. Nicholson, PhD; J. Bruce Morton, PhD; Marco Leyton, PhD
Integer Cystatin C Values: Impact on Discordance Group Assignment and Accuracy of GFR-Estimating Equations
Authors: Dion Groothof, Naser B.N. Shehab, Nicole S. Erler, Stephan J.L. Bakker
Journal: Journal of the American Society of Nephrology (2023)

Fu et al.1 recently reported that eGFR based on both creatinine and cystatin C (eGFRcr-cys) outperforms eGFR derived from creatinine (eGFRcr) or cystatin C (eGFRcys) when eGFRcr and eGFRcys are discordant. Importantly, they presented cystatin C values as integers, a less informative format than the typically used real numbers,2,3 especially when moving from zero to one decimal. Use of integers may affect the accuracy of eGFRcys and eGFRcr-cys and thereby the assignment of participants to discordance groups, potentially invalidating conclusions. To explore this, we performed similar analyses to Fu et al.1 using 698 participants (49.8% male) with available data on iothalamate clearance. Mean (SD) age and iothalamate clearance were 57.5 (11.1) years and 81.4 (28.0) ml/min per 1.73 m2, respectively. Median (25th; 75th percentile) serum creatinine and cystatin C were 94.0 (78.3 to 117.0) μmol/L and 1.07 (0.88 to 1.29) mg/L, respectively. It is unclear whether they stratified bootstrapping by discordance groups—a critical step because its omission can impair performance of GFR-estimating equations by changing proportions of participants within discordance groups. We specifically focused our stratified bootstrap analysis on the eGFRcys>eGFRcr discordance group because this group represents participants with above-average muscle mass4 and contained the fewest samples (8%) in the original study.1 Use of cystatin C as integers or values with one or two decimals resulted in respective assignment of 168, 109, and 113 participants to the eGFRcys>eGFRcr discordance group, consistent with the substantial effect of omitting the first decimal of cystatin C values. When using integers or values with one or two decimals, respective median (95% confidence interval) biases for eGFRcys were 4.19 (1.05 to 6.94), −0.45 (−3.48 to 6.13), and −0.49 (−3.60 to 3.56) ml/min per 1.73 m2. For eGFRcr-cys, these biases were −4.06 (−5.51 to −1.29), −6.77 (−10.79 to −2.47), and −6.21 (−10.96 to −2.66) ml/min per 1.73 m2. For eGFRcr, these biases were −16.23 (−17.49 to −14.19), −20.75 (−24.01 to −15.31), and −21.05 (−24.41 to −15.34) ml/min per 1.73 m2. It seems that rounding cystatin C values to integers may substantially affect both the size of discordance groups and the resulting biases, not only of eGFRcys and eGFRcr-cys, with largest differences when moving from zero to one decimal but also for eGFRcr, albeit in the opposite direction. This suggests potential skewing of the conclusions of Fu et al.1 favoring eGFRcr over eGFRcys. If Fu et al. have cystatin C values with at least one decimal, we encourage them to report on the performance of GFR-estimating equations using these values. Alternatively, for comparability, they could use integers for both cystatin C and creatinine values in mg/dl.
Prediction of High-Risk Donors for Kidney Discard and Nonrecovery Using Structured Donor Characteristics and Unstructured Donor Narratives
Authors: Junichiro Sageshima, Peter Than, Naeem Goussous, Neal Mineyev, Richard Perez
Journal: JAMA Surgery (2023)

Despite the unmet need, many deceased-donor kidneys are discarded or not recovered. Inefficient allocation and prolonged ischemia time are contributing factors, and early detection of high-risk donors may reduce organ loss.
Common Statins Appear to Have Similar Effectiveness
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions
Authors: Cailin E. Deal, Angelene F. Richards, Tracy Yeung, Max J. Maron, Ziqiu Wang, Yen-Ting Lai, Brian R. Fritz, Sunny Himansu, Elisabeth Narayanan, Ding Liu, Rositsa Koleva, Stuart Licht, Chiaowen J. Hsiao, Ivana L. Rajlic, Hillary Koch, Michael Kleyman, Mark E. Pulse, William J. Weiss, Jennifer E. Doering, Samantha K. Lindberg, Nicholas J. Mantis, Andrea Carfi, Obadiah J. Plante
Journal: Cell Reports Medicine (2023)

Colonization of the gut and airways by pathogenic bacteria can lead to local tissue destruction and life-threatening systemic infections, especially in immunologically compromised individuals. Here, we describe an mRNA-based platform enabling delivery of pathogen-specific immunoglobulin A (IgA) monoclonal antibodies into mucosal secretions. The platform consists of synthetic mRNA encoding IgA heavy, light, and joining (J) chains, packaged in lipid nanoparticles (LNPs) that express glycosylated, dimeric IgA with functional activity in vitro and in vivo. Importantly, mRNA-derived IgA had a significantly greater serum half-life and a more native glycosylation profile in mice than did a recombinantly produced IgA. Expression of an mRNA encoded Salmonella-specific IgA in mice resulted in intestinal localization and limited Peyer's patch invasion. The same mRNA-LNP technology was used to express a Pseudomonas-specific IgA that protected from a lung challenge. Leveraging the mRNA antibody technology as a means to intercept bacterial pathogens at mucosal surfaces opens up avenues for prophylactic and therapeutic interventions.
Opportunities to Interrupt Transmission of Enteropathogens of Poultry Origin in Maputo, Mozambique: A Transmission Model Analysis
Authors: Kayoko Shioda, Andrew F. Brouwer, Frederica Lamar, Hermógenes N. Mucache, Karen Levy, Matthew C. Freeman
Journal: Environmental Health Perspectives (2023)

Background: The burden of diarrheal diseases remains high among children in low-income countries. Enteropathogens are challenging to control because they are transmitted via multiple pathways. Chickens are an important animal protein source, but live chickens and their products are often highly contaminated with enteropathogens. Objectives: We conducted this study to a) understand the contribution of multiple transmission pathways to the force of infection of Campylobacter spp. and nontyphoidal Salmonella spp., b) quantify the potential impact of reducing each pathway on human infection, and c) quantify hypothesized pathway reduction from the context of Maputo, Mozambique. Methods: We developed transmission models for Campylobacter and Salmonella that captured person-to-person, water-to-person, food-to-person, soil-to-person, animal-to-person, and all-other-sources-to-person in an urban, low-income setting in Mozambique. We calibrated these models using prevalence data from Maputo, Mozambique and estimates of attributable fraction of transmission pathways for the region. We simulated the prevalence of human infection after reducing transmission through each pathway. Results: Simulation results indicated that if foodborne transmission were reduced by 90%, the prevalence of Campylobacter and Salmonella infection would decline by [52.2%; 95% credible interval (CrI): 39.7, 63.8] and (46.9%; 95% CrI: 39, 55.4), respectively. Interruption of any other pathway did not have a substantial impact. Combined with survey and microbiology data, if contamination of broiler chicken meat at informal markets in Maputo could be reduced by 90%, the total infection of Campylobacter and Salmonella could be reduced by 21% (16–26%) and 12% (10–13%), respectively. Discussion: Our transmission models showed that the foodborne transmission has to be reduced to control enteropathogen infections in our study site, and likely in other similar contexts, but mitigation of this transmission pathway has not received sufficient attention. Our model can serve as a tool to identify effective mitigation opportunities to control zoonotic enteropathogens. https://doi.org/10.1289/EHP12314
Adults With ADHD Might Have Higher Dementia Risk
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Successful Treatment of Eosinophilic Pustular Folliculitis With Dupilumab
Authors: Marie Ottavi, Marine Velin, Nathalie Cardot Leccia, Thierry Passeron
Journal: JAMA Dermatology (2023)

This case report describes a woman in her 20s who presented with an itchy erythematous-papulo-pustular eruption of the scalp for 3 months with progressive centrifugal extension to the face and was diagnosed with Ofuji disease.